肿瘤坏死因子拮抗剂对异丙肾上腺素诱导大鼠心力衰竭的治疗作用

The protection effect of tumor necrosis factor-α antagonist on isoproterenol-induced heart failure in rats

目的 研究肿瘤坏死因子 (TNF α)拮抗剂 (Enbrel,EB)对异丙肾上腺素 (isoproterenol,ISO)诱导大鼠心功能不全和心室重构的治疗作用并探讨其机理。方法 将 70只雄性Wistar大鼠随机分为 3组。EB组 (n =30 ) :给予致心力衰竭剂量ISO后再给予EB治疗 ;ISO组 (n =30 ) :给予ISO后不给予EB治疗 ;对照组 (n =1 0 ) :不给予任何处置。 8周后 ,随机从各组选取存活大鼠 8只 ,进行心脏超声检查和血流动力学测定 ,并测定血清及心肌组织中TNF α、白细胞介素 1 β(IL 1 β)的含量。 结果 (1 )EB组与ISO组相比除左室后壁厚度、左室重量 /体重比值无明显差别外 ,左室舒张末期直径、左室收缩末期直径、左室舒张末压、左室压力最大下降速率、左室等容舒张时间常数均有明显减少 (P <0 0 5) ,而左室短轴缩短率、左室收缩末压、左室压力最大上升速率明显高于ISO组 (P <0 0 1 ) ,但与对照组仍有明显差距。 (2 )EB组血清及心肌组织TNF α与ISO组间无显著差异 (P >0 1 ) ,但显著高于对照组 (P <0 0 1 )。对照组血清TNF α水平未能测出。EB组心肌组织IL 1 β显著低于ISO组 (P <0 0 5) ,对照组心肌组织中及 3组动物血清中IL 1 β均未能测出。 结论 (1 )EB能够明显改善ISO诱导的左室功能不全 ,这除了与其直接拮抗TNF

Objective To study whether Enbrel(EB), a tumor necrosis factor α(TNF α) antagonist ,has the treatment effect on isoproterenol(ISO) induced heart failure and remodeling in rats and to probe its mechanism Methods Seventy adult male Wistar rats were randomly divided into three groups The rats in EB group ( n =30) received two subcutaneous injections (170 mg/kg) of ISO, which were separated by a 24 hour interval and began to receive EB (0 36 mg/kg) subcutaneously 24 hours later twice a week The rats in ISO group ( n =30) also received ISO as described above and began to receive saline (1 ml/kg) subcutaneously 24 hours later twice a week The rats in control group ( n =10) were not administrated Eight weeks after the completion of the ISO injection ,echocardiogram, hemodynamic measurement and the detection of TNF α and interleukin 1β(IL 1β)level in plasma and left ventricular were carried out Results Left ventricular end diastolic diameter, left ventricular end systolic diameter, left ventricular end diastolic pressure (P ED ), dp/dt min ,time constant of left ventricular relaxation(Tc)in EB group were significantly less than those in ISO group( P <0 05), whereas left ventricular fractional shortening, left ventricular end systolic pressure(P ES ),dp/dt max were significantly larger ( P <0 01) than those in ISO group There were no significant differences of left ventricular posterior wall diameter and the ratio of left ventricular weight to body weight between the two groups However, when compared with the control group, there is still a gap The serum and left ventricular TNF α in EB group did not have significant differences compared with ISO group ( P >0 1),but they were significantly higher than those in control group The serum TNF α could not be detected in control group The left ventricular IL 1β level in EB group was significantly lower than that in control group( P <0 05),and it could not be detected in control group The serum IL 1β could not be detected in all groups Conclusion EB could greatly improve the ISO induced cardiac dysfunction The improvement might be partly due to the decrease of the IL 1β level of left ventricular beside the direct block effect of EB on TNF α EB could alleviate the cardiac remodeling by its effect on left ventricular conformation